The central goal of this study is to examine physiological and emotional reactivity to social and gay- related stressors among sexual minority girls (SMGs; girls who report same-sex attraction, same-sex sexual behavior, and/or a bisexual or lesbian identity), and their prospective associations with substance use and abuse. Minority Stress Theory (MST; Meyer, 2003) asserts that discrimination, violence, and victimization are the primary driving mechanisms of substance use and other mental health disparities among SMGs. Several recent studies published by the proposed PI support this hypothesis. Meta-analysis results showed that compared with heterosexual girls, SMGs were 400% more likely to have used drugs and alcohol (Marshal et al 2008), and trajectory analyses show that this disparity is likely to increase as SMGs transition to young adulthood (Marshal et al 2009, 2012). Two other studies showed that compared with heterosexual girls, SMGs were almost 300% more likely to experience suicidality and over 300% more likely to report being assaulted at school (Friedman, Marshal, et al., 2011; Marshal et al, 2011). This study will recruit 120 adolescent girls ages 14-18 (50% SMGs, 50% African-American) to address the proposed aims. We are proposing a modified minority stress model, asserting that physiological and emotional stress reactivity are important components of the minority stress process, and mediators of the pathway to substance use and other mental health outcomes among SMGs. Our specific aims are to: (1) use ecological momentary assessment (EMA) to document the daily social and gay-related stressors examine the real time links between these stressors and substance use, depression, and HIV risk behavior; (2) determine whether SMGs exhibit altered physiological and subjective responses to lab-based social and gay-related stress tasks; and (3) determine whether chronic stress exposure and biomarkers of stress reactivity predict long-term substance use, HIV risk behaviors, and other mental health outcomes. This will be the first study to assess, document, and describe stress reactivity processes among SMGs using lab-based and ecologically valid EMA methodologies. There are no empirically supported substance use interventions for sexual minority youth. Results from this study will accelerate progress towards the development of much needed prevention and intervention programs for SMGs at risk.